Research into a functional cure for HIV in neonates: the need for ethical foresight.

In 2013, researchers announced that a newborn child from Mississippi, USA might have been functionally cured of HIV by being given combination antiretroviral therapy within hours of birth. Public and media attention has since been captured by the possibility of finding a cure for HIV transmitted from mother to child. Research into the strategy used for the Mississippi patient is crucially important to establish whether it can be replicated and shown to work in diverse populations. At the same time, any ethical issues likely to arise in such studies should be addressed and not ignored in the pursuit of a functional cure. In this Personal View we identify ethical issues that could arise in research towards achievment of a functional cure for HIV in neonates, including difficult trade-offs associated with choosing the study population and questions about the broader social implications of the research, and propose ways to resolve them.

Absence of detectable HIV-1 viremia after treatment cessation in an infant.

An infant born to a woman with human immunodeficiency virus type 1 (HIV-1) infection began receiving antiretroviral therapy (ART) 30 hours after birth owing to high-risk exposure. ART was continued when detection of HIV-1 DNA and RNA on repeat testing met the standard diagnostic criteria for infection. After therapy was discontinued (when the child was 18 months of age), levels of plasma HIV-1 RNA, proviral DNA in peripheral-blood mononuclear cells, and HIV-1 antibodies, as assessed by means of clinical assays, remained undetectable in the child through 30 months of age. This case suggests that very early ART in infants may alter the establishment and long-term persistence of HIV-1 infection.

Before and after Silent Spring: from chemical pesticides to biological control and integrated pest management--Britain, 1945-1980.

The use of chemical pesticides increased considerably after World War II, and ecological damage was noticeable by the late 1940s. This paper outlines some ecological problems experienced during the post-war period in the UK, and in parts of what is now Malaysia. Also discussed is the government's response. Although Rachel Carson's book, Silent Spring (1962), was important in bringing the problems to a wider public, she was not alone in sounding the alarm. Pressure from the public and from British scientists led, among other things, to the founding of the Natural Environment Research Council in 1965. By the 1970s, environmentalism was an important movement, and funding for ecological and environmental research was forthcoming even during the economic recession. Some of the recipients were ecologists working at Imperial College London. Moved by the political climate, and by the evidence of ecological damage, they carried out research on the biological control of insect pests.

Chemist, entomologist, Darwinian, and man of affairs: Raphael Meldola and the making of a scientific career.

Raphael Meldola FRS (1849-1915) was professor of chemistry at the City and Guilds Technical College in Finsbury. He was a colleague and close friend of Silvanus Phillips Thompson FRS (1851-1916), the college principal and professor of physics. This paper follows an earlier one on Thompson and the making of his career. It is intended to illustrate further the ways in which scientists of Meldola and Thompson's generation gained advancement within the scientific community. Meldola had interests beyond chemistry, including a serious interest in field entomology. In this he had several well-known mentors including Alfred Russel Wallace and Charles Darwin. The paper, which includes much new information derived from archival work, is presented as six thematic narratives related, among other things, to chemical and technical education, dye chemistry, the Royal Society solar eclipse expedition of 1875, natural history and Darwinism, field clubs, learned societies, and the honouring of scientists. Together these narratives illustrate a generalist/voluntarist career pattern that came to an end with the First World War.

Streptococcus agalactiae myositis in a child with perinatally acquired human immnodeficiency virus.

Pyomyositis is a musculoskeletal infection with formation of an intramuscular abscess. Endemic in tropical climates, it is being reported with increasing frequency in temperate climates such as the United States. The most common causative organism is Staphylococcus aureus, present in greater than 90% of reported cases. Risk factors include underlying chronic illness, malnutrition, immunocompromised state, and muscle trauma. We present a case in which Streptococcus agalactae was the causative agent of myositis in a child with a history of perinatally derived human immunodeficiency virus infection.

Immunoglobulin G kappa [IgG kappa] and IgG lambda paraproteinemia in a child with AIDS and response to highly active antiretroviral therapy.

We report an 8-year-old boy with AIDS, extremely elevated serum immunoglobulin G (IgG) concentration and IgG kappa [IgG(kappa)] and IgG lambda [IgG(lambda)] paraproteinemia. This paraproteinemia partially responded to highly active antiretroviral therapy. This case emphasizes the importance of controlling B-cell activation.

Cryptococcal sepsis diagnosed by bone marrow examination.

Disseminated cryptococcal disease is often associated with immunodeficient states. The diagnosis is usually made using standard antigen tests on serum and cerebrospinal fluid in patients with known immunodeficiency. Often, blood and cerebrospinal fluid cultures also yield Cryptococcus neoformans. The authors describe a child whose diagnosis remained elusive until a bone marrow aspiration, performed as part of an evaluation for suspected neoplasm, revealed the offending organism.

Pharmacokinetics and tolerance of zidovudine in preterm infants.

OBJECTIVE: To determine zidovudine pharmacokinetics and tolerance in premature human human immunodeficiency virus-exposed infants. STUDY DESIGN: Pediatric AIDS Clinical Trials Group Study 331 was a multicentered prospective, open-label study of the use of zidovudine in premature infants. Thirty-eight infants <35 weeks' gestational age (GA) were studied while receiving zidovudine 1.5 mg/kg every 12 hours until 2 weeks of age, then 2.0 mg/kg every 8 hours until 6 weeks of age. Population pharmacokinetics were evaluated at 1, 2, and 4 weeks' postnatal age; zidovudine doses were adjusted to maintain troughs <3 microM. RESULTS: Zidovudine clearance was lower than reported in term infants at similar postnatal ages. Nine premature infants required dose reduction because of high levels (7/19 <30 weeks' and 2/19 >/=30 weeks' GA). Postnatal age, GA, serum creatinine, and furosemide use independently predicted zidovudine clearance. Zidovudine was generally well tolerated in this high-risk population. CONCLUSIONS: Zidovudine clearance is greatly reduced in premature infants. We recommend the following zidovudine dosing schedule in this population: 1.5 mg/kg (intravenous) or 2.0 mg/kg (oral) every 12 hours increased to every 8 hours at 2 weeks of age (>/=30 weeks' GA) or at 4 weeks (<30 weeks' GA).